pubmed.ncbi.nlm.nih.gov

Metformin and the gastrointestinal tract - PubMed

Review

Metformin and the gastrointestinal tract

Laura J McCreight et al. Diabetologia. 2016 Mar.

Abstract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance.

Keywords: Bile acids; DPP-4; GLP-1; Gut/intestine; Lactate; Metformin; Microbiome; OCT1; Review; Serotonin; Uptake.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1

Some of the actions of metformin within the GI tract. The upward arrows indicate increases. DPP4, dipeptidyl peptidase-4; FXR, farnesoid X receptor; FDG, fluorodeoxyglucose; GLP-1, glucagon-like peptide-1; OCT, organic cation transporter; PMAT, plasma membrane monoamine transporter; SERT, serotonin transporter

Fig. 2
Fig. 2

Species abundance in the microbiome of women with type 2 diabetes (T2D) who are treated with metformin (x-axis) or who are not metformin treated (y-axis). Grey spots represent species that do not differ by metformin exposure. Coloured dots represent species differing by metformin exposure, with the colour representing the bacterial species shown in the key. Figure from Karlsson et al, Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013;498:99–103. Reproduced with permission from Nature Publishing Group

Similar articles

Cited by

References

    1. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care. 1989;12:553–564. doi: 10.2337/diacare.12.8.553. - DOI - PubMed
    1. Bailey CJ, Day C. Metformin: its botanical background. Pract Diabetes Int. 2004;21:115–117. doi: 10.1002/pdi.606. - DOI
    1. Inzucchi SI, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58:429–442. doi: 10.1007/s00125-014-3460-0. - DOI - PubMed
    1. Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011;50:81–98. doi: 10.2165/11534750-000000000-00000. - DOI - PubMed
    1. Innzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312:2668–2675. doi: 10.1001/jama.2014.15298. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources